Recurrent Endometrial Cancer Clinical Trial
Official title:
A Phase I Study of Lapatinib (Tykerb) Plus Ixabepilone (Ixempra) as 2nd-line Treatment for Patients With HER-2 Overexpressed Recurrent or Persistent Endometrial Carcinoma or Carcinosarcoma
Verified date | October 2011 |
Source | Chang Gung Memorial Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | Taiwan: Department of Health |
Study type | Interventional |
Endometrial cancer (EC) is the 8th most common female cancer in Taiwan. Its incidence is
increasing in the recent few years, around 1,200 new cases per year. The outcome of
recurrent EC is disappointing, except focal recurrences that could be irradiated or removed.
Chemotherapy is currently the most common salvage treatment for recurrent endometrial
cancer. However, the response rate (RR) to 2nd-line treatment is approximately 0-27.3%, with
short median time to progression, 2-3.9 months and low overall survival, 6.4-11 months.
Due to progress of studies on the molecular and genetic basis of cancer and cellular
signaling pathways, targeted therapy has been developed for various cancer treatments. A
Gynecologic Oncology Group study found 44% of advanced endometrial cancer had HER>=2+ and
the ratio of HER2:chromosome 17 (CEP17) >=2. Another study showed that HER>=2+ was seen in
47% of carcinosarcoma. These evidences indicated HER2 gene amplification and HER2
overexpression occur in endometrial cancer and carcinosarcoma, especially in those of high
grade and recurrence. Lapatinib (L), an oral inhibitor of both EGFR(epidermal growth factor
receptor) and HER2(human epidermal growth receptor), has been shown to be an effective
treatment in HER2/neu overexpressing metastatic breast cancer. Ixabepilone is a
semisynthetic analog of the natural product epothilone B, and recently has been approved by
US Food and Drug Administration as a treatment option in metastatic breast cancer. It was
also observed that lapatinib + ixabepilone killed more breast tumor cells than trastuzumab +
paclitaxel in vitro. Two GOG(Gynecologic Oncology Group) studies had reported that weekly
Ixabepilone as 2nd-line chemotherapy provided a similar RR to 3-weekly regimen of 14.3% in
platinum- and taxane-resistant epithelial ovarian cancer with less severe toxicities. The
combination of lapatinib and ixabepilone is expected to become an effective treatment for
recurrent endometrial cancer and carcinosarcoma, but the ideal dose is yet to be surveyed.
Status | Enrolling by invitation |
Enrollment | 24 |
Est. completion date | April 2014 |
Est. primary completion date | April 2013 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 20 Years to 75 Years |
Eligibility |
Inclusion Criteria: 1. Histologically confirmed carcinoma or carcinosarcoma of the endometrium with evidence of persistent disease or progression after initial surgery and adjuvant chemotherapy, radiotherapy, or both, not amenable for curative salvage therapy. 2. ErbB2 gene amplification by FISH (ErbB2 gene copies to chromosome 17 signals) of > = 2.0; ErbB2 overexpression is defined by immunostaining >=2 for ErB2 3. Measurable disease, defined as =1 lesions that can be accurately measured in - 1 dimensions as =20 mm by conventional techniques OR as =10 mm by spiral CT scan, MRI or PET scan (those who undergo cytoreductive salvage surgery with residual tumor = 20 mm are eligible) 4. Those who are chemotherapy-naive be enrolled until failing one chemotherapy regimen 5. Prior treatments with radiation therapy for palliative management of metastatic disease is permitted provided that at least 4 weeks have elapsed since the last fraction of radiation therapy, disease progression has been documented and all treatment related adverse events are ? grade 2 at the time of registration. 6. Life expectancy = 12 weeks 7. ECOG(Eastern Cooperative Oncology Group) performance status 0-2 8. Patients must have normal organ and marrow function measured within 14 days Exclusion Criteria: 1. Previously unirradiated, isolated vaginal, pelvic or paraaortic lymph node, lung (which confined to one lobe that can be resected or radiated) recurrence or other potentially curable recurrence such as central pelvic recurrence for which a pelvic exenteration is feasible 2. Pregnant or lactating women. 3. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 4. Prior therapy with Lapatinib or Ixabepilone. 5. CNS metastases. 6. Ongoing other concurrent investigational agents or anticancer therapy 7. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious non- healing wound/ulcer/bone fracture, or psychiatric illness/social situations that would limit compliance with study requirements. 8. Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis). 9. Preexisting peripheral neuropathy=G2 |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Hung-Hsueh Chou | Bristol-Myers Squibb, GlaxoSmithKline |
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Determine the Maximum Tolerated Dosage (MTD) of the combination of lapatinib with Ixabepilone as 2nd-line chemotherapy in patients with treatment in HER2 overexpressed recurrent or persistent endometrial cancer or carcinosarcoma | Determine the Maximum Tolerated Dosage (MTD) of the combination of lapatinib with Ixabepilone as 2nd-line chemotherapy in patients with treatment in HER2 overexpressed recurrent or persistent endometrial cancer or carcinosarcoma. | 2013/Apr | Yes |
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